3. Genetic code coevolution.
The results support the view that the genetic code evolved under simultaneous constraints from RNA coding and protein folding. Codon assignments were not arbitrary but co-adapted with the structural properties of early proteins, implying a feedback-driven evolutionary process.
4. Statistical rather than mechanistic.
Importantly, the study is primarily descriptive: it uncovers correlations but does not provide a dynamical model for how such correlations emerged or stabilized over time. This leaves a gap between observed proteomic patterns and explanatory theory. Taken together, these findings reinforce the argument that the genetic code and proteins coevolved rather than emerged independently. The persistence of dipeptide-level signals across proteomes suggests that coevolutionary coupling leaves measurable molecular signatures. What remains missing, however, is a formal mathematical framework capable of explaining how such signatures arise naturally from evolutionary dynamics. This is precisely the gap that our CAS-based model is designed to fill.
B. Genetic code thermostability and protein structure correlations
The relationship between the genetic code and protein structure has long been hypothesized to reflect not only functional requirements but also physicochemical constraints. One particularly compelling line of evidence concerns the correlation between codon assignments and protein thermostability.
1. Codon--amino acid mapping and stability.
Codon choices influence the amino acid composition of proteins, which in turn affects folding stability, aggregation resistance, and robustness under thermal stress. Comparative analyses reveal that synonymous codon usage is often biased toward configurations that favor structural resilience, suggesting that early genetic codes were shaped by thermostability pressures.
2. Dipeptide-level constraints.
At the dipeptide level, certain amino acid pairs appear more frequently than expected by chance, and these patterns correlate with codon pairing rules. These biases are particularly strong in thermophilic organisms, reinforcing the idea that the genetic code coevolved with protein thermostability.
3. Implications for early environments.
